Major role of the soluble interleukin-6/interleukin-6 receptor complex for the proliferation of interleukin-6-dependent human myeloma cell lines.
Interleukin-6 (IL-6) is a proinflammatory cytokine which possesses a central growth factor activity for certain tumor cells such as plasma cells in multiple myeloma (MM). Upon binding of IL-6, soluble IL-6 receptor (sIL-6R) has been shown to retain its affinity for IL-6 and to associate with the signal-transducing gp130 chain. Therefore, contrary to the majority of soluble cytokine receptors, it plays an agonist role in IL-6 signaling. In order to test its physiological importance as compared to that of its membrane counterpart, we studied cells from two myeloma cell lines which need exogenous IL-6 to proliferate and release sIL-6R into their culture supernatant. Using a new culture system where the supernatant recirculated permanently through an anti-IL-6R affinity column, all sIL-6R was removed from the culture medium throughout the culture period. Under these conditions IL-6-dependent cells were unable to grow in the presence of physiological concentrations of IL-6, showing the major role of the sIL-6R for sustaining the proliferation of these cell lines. Increasing IL-6 concentrations well over the physiological values allowed the cells to proliferate again. No effect was seen when sIL-6R was removed from the supernatant of an IL-6-independent myeloma cell line. These results show that the levels of circulating sIL-6R (and thus those of IL-6/sIL-6R complex) are worth looking at in pathologies involving IL-6 hyperactivity.
Gaillard
J P
JP
INSERM U 291, Montpellier, France.
Liautard
J
J
Klein
B
B
Brochier
J
J
D002455:Cell Division / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology*; D019947:Receptors, Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D019947:Receptors, Interleukin-6